Problems in and around the eyelid can be caused by various diseases or conditions. Causes include seborrheic dermatitis (dandruff), the presence of a bacterial infection (commonly Staphylococcus), a blocked oil gland in the eyelid, food, pollen or other allergies, and ocular rosacea.
Eyelid problems can result in blepharitis, which is an inflammation, often chronic, of the eyelid. Blepharitis is one of the most common eye disorders. Blepharitis can occur in two regions of the eye: at the lid margin on the outside front part of the eyelid where the eyelashes grow (referred to as “anterior blepharitis”) and at the inner eyelid where the moist part of the eyelid contacts the eye and the meibomian (oil) glands are located (referred to as “posterior blepharitis”). Symptoms of blepharitis can include a red, itchy, irritated and/or swollen eyelid, crusting of the eyelid upon awakening, a sensation of a foreign body in the eye, a sensation of burning in the eye, sensitivity of the eye to light, and/or loss of eyelashes.
Ocular rosacea is a condition that affects the eyelids and ocular surface. Ocular rosacea is a long term, inflammatory eye disease that can cause blepharitis and, less commonly, conjunctivitis (inflammation or infection of the conjunctiva that lines the eyelid and part of the eyeball). The presence of ocular rosacea is commonly characterized by irritation, dryness, redness in the eyes, grittiness in the eyes, and/or blurry vision. In more severe cases of ocular rosacea, lid margin and conjunctival telangiectasias (appearance of blood vessels near the surface), eyelid crusts, eyelid scales, corneal infiltrates, corneal ulcers, vascularization, and on occasion, sight-threatening disease occur.
By some estimates, appearance of ocular rosacea correlates with the presence of facial rosacea about 50% of the time. Facial rosacea is a chronic skin condition involving abnormality in the sebaceous glands of the face and eyelids. Facial rosacea occurs on the forehead, cheeks, and nose and is divided into several subtypes, erythematotelangiectatic rosacea (characterized by redness, flushing, and telangiectasias, which is appearance of small blood vessels); papulopustular rosacea, (characterized by small bumps and pus filled lesions-including the presence of papules which are elevations of the skin without fluid) and pustules which are small, inflamed, pus filled, blister like lesions on the skin surface); and phymatous rosacea (characterized by thickened, bumpy skin).
Facial rosacea can affect anyone, but commonly starts in a person after about age 30, and preferentially affects individuals with light colored skin. Facial rosacea is widespread, with an estimated 10% of the American population exhibiting symptoms.
The exact cause(s) of facial and/or ocular rosacea are not known. Cold or windy weather, genetic factors, hot baths, infection with the bacteria Helicobacter pylori (commonly associated with the presence of stomach ulcers), side effects of certain medications, ingestion of hot or spicy foods or drinks, stress, sun exposure, and the presence of Demodex folliculorum or Demodex brevis on the skin of the face and/or eyelid have been proposed as possible causes or triggers for rosacea.
The arthropod Demodex is a tiny ectoparasitic mite that lives in or near skin, hair and eyelash follicles of mammals, including humans. The two species D. folliculorum and D. brevis can co-exist in the face and eyelids, although D. brevis in particular tends to burrow into the eyelash sebaceous glands and the meibomian glands, where it lays eggs. Larvae hatch after about 4 days, and take another seven days to develop into adults. The lifespan of a mite is several weeks. Some data suggest that Demodex mites may harbor the bacterium Bacillus oleronius. One mechanism that has been hypothesized to explain how the presence of Demodex might correlate with rosacea is that the human immune system responds to proteins produced by B. oleronius, resulting in inflammation (see, e.g., Li et al., “Correlation between ocular Demodex infestation and serum immunoreactivity to Bacillus proteins in patients with facial rosacea”, Ophthalmology 2010; 117:870-877 and references therein).
Although sometimes referred to as “acne rosacea” and confused with acne vulgaris (referred to commonly as “acne”) because both cause irritation to the face, facial rosacea and acne are different, and therefore the treatments recommended to manage them are also different.
Acne is the most common skin condition in the United States. While it can occur at any age, it most commonly affects teenagers and young adults. Facial rosacea is distinguished from acne vulgaris by the presence of non-inflammatory comedones (follicles filled with sebum and sloughed off cells; commonly referred to as “whiteheads” and “blackheads”) with acne and their absence in facial rosacea.
Although acne and rosacea sometimes co-exist in skin, they often occur do not overlap and dermatologists recommend different protocols for treatment of rosacea and acne. The goals with acne treatments are to reduce oil production, speed up skin turnover, control bacterial infection and reduce inflammation. In addition to cleansing the skin, acne may be treated with application of acetone, alcohol, antibiotics, astringents, benzoyl peroxide, retinoids and salicylic acid, and/or ingestion of oral antibiotics, and, for women, ingestion of oral contraceptives. Techniques that cause exfoliation, such as chemical peels and microdermabrasion, may be used.
The effects of acne may be reduced but not eliminated by applying a sufficient amount of tea tree oil. Enshaieh et al. (Indian J. Dermatol Venereol Leprol. 2007, January-February: 73(1):22-25) describe the difficulties of obtaining an acne treatment medicine that has an effect and is tolerated by patients. Enshaieh et al. report use of 5% tea tree oil to treat mild to moderate acne vulgaris and found that 5% tea tree oil was 3.55 times more effective in improving total acne lesions and 5.75 times more effective in reducing acne severity as measured by the Acne Severity Index (ASI). Bassett et al. (Med J Aus), 1990 Oct. 15, 153(8):455-8 examined the effectiveness of 5% tea tree oil in reducing the number of inflamed and non-inflamed lesions in patients with acne. Application of 5% tea tree oil for twenty minutes two times a day for 45 minutes to patients suffering from acne reduced the number of lesions. The tea tree oil acted more slowly than the acne treatment (benzoyl peroxide) to which it was compared. Of note, even using frequent (e.g. twice daily) and relatively long application times over the course of many weeks, 5% tea tree oil treatment was of limited efficacy in treating acne.
U.S. Patent Publication 2005/0037034 to Rhoades describes a composition for treating comedonal acne associated with acne vulgaris and inflammatory acne. The composition contains an acne treatment agent together with abrasive particles in a base. A method of using the agent is described. The face is buffed or otherwise treated with the agent using, for example, a hand-held vibratory device. The acne treatment agent can be, for example, benzoyl peroxide, salicylic acid, retinol, hydroxyl acid, or tea tree oil.
Increasingly aggressive acne treatment modalities may be used, as shown by the use of oral medications such as isotretinoin, which has significant side effects on the entire body for individuals whose acne cannot be managed by other methods. Simple, effective and safe acne treatments are still lacking.
These acne treatments tend to be harsh, and harsh treatments have traditionally been thought to worsen the symptoms of rosacea. In particular, because skin affected with facial rosacea is easily irritated, the American Academy of Dermatologists (AAD) recommends gentle face washing for patients. The skin should not be rubbed or scrubbed. Even use of a bath puff or washcloth is discouraged as it can be irritating. Use of alcohol, astringents, clove oil, eucalyptus oil, exfoliants, fragrance, peppermint, salicylic acid, toners, and witch hazel has typically been discouraged.
Facial rosacea patients are advised to avoid “trigger” factors. Topical or oral antibiotics may be prescribed, although it is thought that these are effective due to their anti-inflammatory properties, rather than through their antibiotic properties. Laser treatment may be used to reduce the appearance of blood vessels or other redness in the face.
Treatments of facial and ocular rosacea and blepharitis range from simple over-the-counter treatments to treatment from a dermatologist or ophthalmologist, depending on the severity and duration of the symptoms.
Over-the-counter treatments to relieve the symptoms of ocular rosacea and non-rosacea blepharitis include variations of basic washing and massaging routines. In one typical protocol, the eyelids are cleaned and massaged one or more times a day. First a warm, soft compress is applied to the eyelid for 5-10 minutes. This treatment is thought to loosen the lipids in the meibomian glands. Next, the eyelids are cleaned by gently sliding a cotton swab soaked with dilute baby shampoo across the lid margins. Next, the eyelids can be massaged using a finger or swab moving across the eyelid. While there is individual variation, these treatments may generally be performed over of the course of weeks to months to eliminate or reduce the symptoms of blepharitis. Symptoms of blepharitis tend to recur after this type of treatment and require an additional round or rounds of treatment or a different treatment.
In ocular rosacea cases (and in non-rosacea blepharitis cases) did not respond to the wash and massage treatments, other treatments have been tried. Patients have been treated with medications to manage the inflammation (e.g., eye drops containing corticosteroids), topical or oral antibiotics (e.g., doxycycline, gentamicin, tetracycline, azithromycin) to eliminate bacterial infection, surgery, or chemicals to try to control Demodex infestation.
U.S. Patent Publication 2007/0203462 to Soroudi and U.S. Patent Publication 2009/0137533 to Adkins describe eyelid treatment kits for improving eyelid hygiene and treating infection and inflammation using antibiotics to eliminate bacterial infection. The kits are meant for treating infection (e.g., blepharitis, meibomitis, acute dacryocystitis, orbital or preseptal cellulitis), treating inflammation (e.g., hordeola, chalazia, or contact dermatitis), treating dry eyes, and/or as post-operative treatment. The kit contains a low dose of an antibiotic (doxycline) and a non-irritating eyelid cleansing composition. Soroudi describes an improved method and materials for use in order to apply heat to the peri-ocular region using a soft, non-abrasive, lint free material such as gauze. The material may contain antibiotics and a cleaner that is gentle to the skin, such as baby shampoo. This material is applied to the eyelid in order to remove bacteria and decrease inflammation.
Other treatments for Demodex involve applying volatile liquids such as ether and alcohol to the eyelid to try to kill the mites. However, there are toxicity concerns with use of these chemicals. Additionally, they were not effective at eliminating blepharitis.
Other treatments for blepharitis associated with a Demodex infestation involve spreading an ointment containing 1% mercury oxide or 2% metronidazole gel or Pilocarpine at the base of the eyelashes. The purpose is to entrap mites as they emerge from the follicle at night.
Kaoukhov et al., U.S. Patent Publication 2009/0093421, describes compositions for the treatment of ophthalmic pathologies, including ocular rosacea thought to be caused by infestation of Demodex, using the anti-parasitic agents avermectin and/or milbemycin. The compositions can be applied directly to the eye, or can be solid forms deployed at the surface of the eye in the form of impregnated pads, snydets, and wipes. Kaoukhov lists various additives that can be included in the compositions, including wetting agents, agents for improving flavor, preservatives, stabilizing agents, agents for regulating moisture, pH-regulating agents; buffers; agents for modifying osmotic pressure; emulsifying agents; agents for increasing viscosity; and antioxidants. The efficacy of this as a topical application is unknown and possible side effects due to the use of avermectin and milbemycin are a concern.
More recently, tea tree oil was tested as a treatment for ocular rosacea. Tea tree oil was originally obtained by steam distillation of the leaves of the Melaleuca family of trees, and especially from Melaleuca alternifolia, a tree native to Australia. Tea tree oil can be extracted from members of the Myrtaceae family, including Melaleuca alternifolia, Melaleuca linafolia, and Melaleuca dissitiflora. Tea tree oil contains terpenes (pinenes, terpinene, and cymene), cineole, and an alcohol terpinol. It was used as a traditional medicine to prevent and treat infections. It is thought to have antiseptic, antifungal, and antibacterial properties.
Work from Schaffer C G Tseng (Gao et al., “In vitro and in vivo killing of Demodex by tea tree oil”, British J of Ophthalmology (2005) 89:1468-1473; Gao et al., Cornea “Clinical treatment of ocular demodecosis by lid scrub with tea tree oil (February 2007): Vol. 26(2); Gao et al. U.S. Patent Application Publication 2009/0214676; Gao et al. U.S. Patent Application Publication 2009/0061025; Li et al. “Correlation between ocular Demodex infestation and serum immunoreactivity to Bacillus proteins in patients with facial rosacea”, Ophthalmology 2010; 117:870-877) describe reagents, tests, and treatment for patients harboring ocular Demodex. The authors found that application of tea tree oil, caraway oil, and dill weed oil in vitro would kill Demodex. The treatment uses a high concentration of tea tree oil (e.g., 50%) in baby shampoo. The protocol involves cleaning the eyelids and eyelashes with a composition at the doctor's office using a cotton tip wetted in baby shampoo containing 50% tea tree oil. The recommended regimen of six strokes is repeated three times, with a 5-10 minute rest and stroke with a dry cotton tip to remove excess tea tree oil between repeats. The protocol is performed weekly (e.g., for 3-9 weeks) at the clinic. In between clinic visits, the patient continues care at home, generally consisting of daily massages of the eyelids (e.g., for 3-5 minutes) with the fingers using diluted tea tree oil (e.g., 5%) in baby shampoo. The treatment was tolerated by many patients; however others felt eyelid irritation and experienced eyelid spasms during the office tea tree oil treatment. Although the combined treatments rid the eyelids of mites in a majority of the cases, the treatments are inconvenient and costly, requiring weekly visits to the doctor or clinic, as well as additional daily treatments for up to three months. Of particular note, several patients whose symptoms had improved were not entirely rid of the Demodex infestations and continued to have symptoms, albeit reduced, of redness, itching, foreign body sensation, dryness, blurry vision, pain, burning sensation and grittiness even after weeks of intensive treatments.
Microdermabrasion is a technique that mechanically ablates skin. It is used on the face, neck or arms to remove dead or damaged skin cells. It speeds the natural process of exfoliation by mechanically removing the uppermost layer of the epidermis. Microdermabrasion makes it easier for skin products to penetrate into the deeper layers of the skin. Epithelialization and collagen production are stimulated. It is used to counteract the effects of acne and photoaging and reduces acne scars, age spots, enlarged pores, fine lines, and the appearance of blemishes, other scars, stretch marks, undesired skin pigmentation, and wrinkles.
Microdermabrasion uses a device to spray fine microcrystals across the skin surface. This treatment causes superficial abrasion that removes a layer of stratum corneum of the skin. Microdermabrasion is currently contraindicated for an individual suffering from rosacea, seborrheic dermatitis, psoriasis, eczema, or vitiligo, and for any use close to the eye or on the eyelid.